In normal men of varying degrees of adiposity, alphaadrenergic blockade (one-hour intravenous infusion with phentolamine, 0.5 mg./min.) produced a 31 ± 23 per cent (mean ± S.D.) increase (n = 6, p < .02) over basal insulin levels whereas beta-adrenergic blockade (one-hour intravenous infusion with propranolol, 0.08 mg./min.) produced a 38 ± 15 per cent decrease (n = 6, p < .002) from basal insulin levels; basal glucose did not change during either type of blockade. Epinephrine (two-hour intravenous infusion, 6 /tg./min.) produced a 46 ± 8 per cent decrement in basal insulin by 7 ± 4 min. (n = 12, p < .001). This was followed by a period of recovery during which insulin levels rose to control levels by 46 ± 26 minutes and to 166 ± 36 per cent of control (p < .001) by two hours. The nadir of the decrement correlated, with a high degree of statistical significance, with basal insulin values (r = .99, p < .001), and the amount of time required during the recovery phase for insulin levels to rise to control levels correlated highly with the nadir of the decrement (r = .83, p < .001). The epinephrine-induced decrement from basal insulin did not occur in three subjects pretreated with phentolamine but did occur in four subjects pretreated with propranolol. In the four subjects pretreated with propranolol, the mean recovery time during epinephrine infusion was seventy-two minutes, compared to thirty-six minutes for the group receiving epinephrine alone. In four separate studies, propranolol was superimposed after two hours of a three-hour epinephrine infusion had elapsed, and the elevated insulin levels that had developed by two hours promptly fell below basal levels. It is concluded that (1) endogenous adrenergic activity modulates basal insulin secretion; (2) increases in circulating epinephrine prompt a rapid, marked fall in basal insulin which is alpha mediated; and (3) a slower, beta-mediated recovery phase follows during which insulin surpasses basal levels.

In this study the penetration of plasma insulin and glucose into the cerebrospinal fluid (CSF) was investigated. Rats were implanted with cannulas in the cisterna magna and into the left and right jugular veins. Freely moving rats were intravenously infused during 4 h with either glucose solution (10 mg/min) or saline. Before, during, and after the infusions, simultaneous blood and CSF samples were taken. Infusion of glucose led to an immediate rise of both plasma glucose and insulin. Although CSF glucose followed plasma glucose within 10 min, CSF insulin was unchanged until 40 min. After termination of the glucose infusion, levels of all substances returned to base line within 10 min. Twenty-four-hour food deprivation resulted in a significant decrease of plasma glucose, plasma insulin, CSF glucose, and CSF insulin. At the onset of eating after deprivation, an increase of plasma glucose and insulin occurred within 10 min, whereas CSF glucose was delayed between 10 and 40 min, after which ad libitum values were attained or surpassed. CSF insulin always remained below ad libitum levels. It is concluded that 1) glucose and insulin penetrate into the CSF and 2) CSF insulin and glucose can fulfill a putative feedback in homeostatic control of food intake and body weight.

To determine which test of islet function is the most sensitive indicator of subclinical beta-cell loss, we studied six conscious dogs before and 1 and 6 wk after removal of the splenic and uncinate lobes [64 +/- 2% pancreatectomy (PX)]. To assess hyperglycemic potentiation, acute insulin secretory responses (AIR) to 5 g i.v. arginine were measured at the fasting plasma glucose (FPG) level after PG was clamped at approximately 250 mg/dl and after PG was clamped at a maximally potentiating level of 550-650 mg/dl. FPG levels were unaffected by PX (112 +/- 4 mg/dl pre-PX vs. 115 +/- 5 mg/dl 6 wk after PX, P NS). Similarly, basal insulin levels remained constant after PX (11 +/- 2 microU/ml pre-PX vs. 11 +/- 1 microU/ml 6 wk after PX, P NS). The AIR to 300 mg/kg i.v. glucose decreased slightly from 42 +/- 9 microU/ml pre-PX to 32 +/- 5 microU/ml 6 wk after PX (P NS), and thus the beta-cell loss was underestimated. In contrast, insulin responses to arginine declined markedly after PX. The AIR to arginine obtained at FPG levels declined from 23 +/- 3 microU/ml pre-PX to 13 +/- 2 microU/ml 6 wk after PX (P = .04). The AIR to arginine obtained at PG levels of approximately 250 mg/dl declined even more, from a pre-PX value of 56 +/- 7 microU/ml to 21 +/- 4 microU/ml 6 wk after PX (P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of intravenous pentobarbital were studied in dogs. Plasma pentobarbital concentrations were inversely related to epinephrine and norepinephrine concentrations. Plasma catecholamines appeared fully suppressed at pentobarbital levels greater than 25-30 micrograms/ml. Furthermore, pentobarbital levels were negatively related to rectal temperature, heart rate, and mean blood pressure. The methods of pentobarbital administration influenced plasma pentobarbital as well as epinephrine and norepinephrine levels, temperature, heart rate, and blood pressure. These observations suggest the possibility that pentobarbital inhibits the sympathetic nervous system, which in turn may affect temperature, heart rate, and blood pressure. Because pentobarbital anesthesia affects plasma catecholamine concentrations, the regimen used in animal models requires consideration when interpreting data potentially influenced by the sympathetic nervous system.

Abstract. A series of studies were performed to determine the relationship between physiologic levels of circulating plasma norepinephrine and epinephrine and human platelet alpha-2 binding site number and the affinity (KD) of these sites for antagonist radioligands. In one study, alpha-2-adrenergic binding site number and affinity were compared using both were significantly changed in six normal subjects when plasma norepinephrine levels increased during oral administration of prazosin for 1 wk. Thus, in a crosssectional analysis and after a change in plasma catecholamine concentrations, there was no relationship in normal subjects between platelet alpha-2 binding site number or affinity of these sites for antagonist radioligands and the circulating catecholamine levels to which the platelets were exposed. 74, September 198474, September , 106374, September -1072 In a group (n = 7) of patients who lack epinephrineinduced platelet aggregation due to abnormal thrombopoiesis, binding site number was decreased (304±36 vs. 572±29 sites/platelet, P < 0.001) and KD tended to be greater (8.69±2.44 vs. 5.40±0.31 nM, P = NS) than in normal subjects (n = 46), despite having similar plasma catecholamine levels. There was no difference in binding site number (491 + 116 sites/platelet) and KD (5.61±0.84 nM) in patients (n = 5) with autonomic insufficiency and low levels of upright plasma norepinephrine when compared with the normal subjects. Two patients were examined before and after the removal of a pheochromocytoma. Their binding site number and KD were normal before the operation and essentially unchanged after the tumor removal and fall of plasma catecholamines.Thus, this study demonstrates that within the physiologic and pathophysiologic range of plasma catecholamines (in men), there is no relationship between the circulating catecholamine concentration and either platelet alpha-2 adrenergic binding site number or the affinity of these sites for antagonist radioligands.